Lipoxygenases specificity, table

Table III. Effect of a lipoxygenase-specific inhibitor on the occurrence of enzymically- and oxidatively-derived volatiles in fish.

Inhibition of PG biosynthesis by open chain diarylheptanoids was first reported by Itokawa and his coworkers (26, 31). Their results were implemented by studies on additional compounds first by Flynn (88) and later by Kinchi et al. (85). The latter group extended the assay of inhibitor activity also to the 5-lipoxygenase enzyme system. Their results are summarized in Table 2. Among macrocyclic diarylheptanoids only for garuganins (88-95), isolated from Garuga pinnata was some antiinflammatory activity claimed, but no specific data were disclosed (57, 58). 

Besides the design of synthetic molecules, several papers reported the presence of specific enzymatic reactions able to produce also in the cells compounds able to act as reversible FAAH inhibitors (Maccarrone and Finazzi-Agro, 2004a). In particular, it has been found that oxidative metabolites of AEA generated by various lipoxygenases, i.e. the hydroxyanandamides (HAEAs see 12-OH-AEA in Table 4.1), are powerful inhibitors of FAAH (van der Stelt et al., 2002). Instead, derivatives of AEA generated by cyclooxygenase-2, and termed prosta-mides, have been recently shown to be inelfective on FAAH activity (Matias et al., 2004). 

Lipoxygenases from plants mostly exhibit 9- or 13-regiospecificity. A LOX with C-8 specificity has been found in a mushroom (Table 3.33). 

Table 1 Substrate specificity of lipoxygenase and Cs-aldehyde-forming activity... 

Of the 8 fatty acids tested as giganteum lipoxygenase substrates (delta 9,12-octadecadienoic, delta 9,12,15-octadecatrienoic, delta 6,9,12-octadecatrienoic, delta 11,14-elcosadienoic, delta 8,11,14-eicosatrienoic, delta 5,8,11,14-eicosatetraenoic, delta 5,8,11,14,17-eicosapentaenoic, and delta 4,7,10,13,16,19-docosahexaenoic acids, all-cis), only arachidonlc (C-20 4), eicosapentaenoic (C-20 5) and docosahexaenoic (C-22 6) acids were consistently metabolized (Table 1). It is noteworthy that the C-18 compounds apparently are not suitable substrates for the giganteum enz5nne under the incubation conditions used. If this initial observation is verified by work in progress, this will be the first documented instance of such selective lipoxygenase substrate specificity. 

Table 1. Substrate Specificity of Lagenidium giganteum Lipoxygenase...

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